Summary: In the mid-1980s we carried out a prospective study of early pregnancy in which we enrolled 221 health women who were planning to become pregnant. These women collected daily urine specimens for up to six months. We've assayed these specimens to describe the hormonal events of the menstrual cycle and early pregnancy. 155 women became clinically pregnant during the study, while 44 had pregnancies that ended so early that the pregnancies were detectable only by assay of urinary human chorionic gonadotropin. This unique study has been called a landmark, and continues to provide a rich resource for the description of the earliest stages of pregnancy. (More than 30,000 urine samples are still being stored.) We've published more than 40 papers from this study over the past two decades, some of which have led to new understanding of the fundamental processes of conception and early pregnancy. Last year's progress. We completed an extensive analysis of human chorionic gonadotropin (hCG) and its variants in early pregnancy. hCG is the primary hormone responsible for signaling the presence of the conceptus after implantation. Intact hCG is usually regarded as the main analyte, both functionally and for the purposes of early detection of pregnancy. We found in fact that the intact form of hCG is subject to wide fluctuations during early pregnancy -- so extreme, in fact, that it raises questions about possible novel mechanisms of molecular recombination as part of this signalling process. This variability may have practical clinical implications, in that it could produce false-negative results on pregnancy tests, and distort estimates of hCG doubling-times (a marker of embryonic health). We conclude that hCG assays which combine several forms of hCG may provide more reliable and more valid measures. In another project completed this year, we assessed the contributions of maternal characteristics and exposures to length of the follicular phase of the menstrual cycle. The time of ovulation in the menstrual cycle is notoriously variable, and yet little is known about the sources of such variability other than that the time from bleeding to the next ovulation (the follicular phase) varies far more than the time from ovulation to the following menses (luteal phase). We found that a history of oral contraceptive use was related to a longer follicular phase, and that recent marijuana use was also related to a longer follicular phase. The marijuana effect is particularly interesting, as there have been animal studies to suggest that the main metabolites of marijuana can affect ovulation.